We live in a society obsessed with overall personal appearance and losing weight. Despite this obsession, medical reports confirm that 68% of all Americans are overweight, and 33% of those past the age of 20 are clinically obese. This equates to 64 million overweight adults in the just the United States alone. Beyond the obvious cosmetic considerations, obesity is one of the leading causes of heart disease, hypertension, stroke, and diabetes, and is a contributing cause in cancer. The size of the market for weight control products is estimated at over $100 billion per annum worldwide and is ever increasing. There clearly is a need for an effective, safe, and palatable weight control product to stop this growing problem.
The medical profession has long proclaimed the benefits of a high fiber, low fat diet. Chitosan has received considerable attention in this context since it can be applied to bind fat in food, creating an indigestible mass that lets the fat pass unabsorbed through an individual's digestive system and right out of the body. Chitosan (i.e., (1.fwdarw.4) 2-amino-2-deoxy-.beta.-D-glucosamine, also known as polyglucosamine) is a water-immiscible biopolymeric compound comprising partially or fully deacetylated chitin. Chitin is a cellulose-like polymer that is present in fugal walls and the exoskeletons of arthropods, including insects, crabs, shrimp, and lobsters. Chitosan can bind up to 4 to 6 times its weight in oils, greases, and toxic substances (Nauss et al., Lipids, 18 (10), 714-719 (1983)). This capacity of chitosan derives from its possession of positively charged amino groups that bind to negatively charged fatty acids (the building blocks of fat) and bile acids (used in making cholesterol).
Chitosan's unique abilities are responsible for its employ as an additive or primary component in numerous applications in the fields of food, health, cosmetics, agriculture, waste-water treatment, as well as in other industries. In the food and health industry, chitosan currently is available in tablet form under several brand names. Also, tablets containing chitosan combined with ascorbic acid are presently marketed. Ascorbic acid acts in synergy with chitosan to provide fat absorption properties which are greatly enhanced over those of chitosan alone. However, chitosan tablets are bulky, need to be taken in large quantities, have an unpleasant taste, and may possess other noticeable side effects. Thus, there is a current need for a product that provides for weight control and is easy to use, particularly in comparison to capsules containing chitosan.
"U.S. Pat. No. 5,736,532 pertains to a fat absorption and cholesterol reduction formulation comprising chitosan and nicotinic acid, and describes the use of this formulation to reduce cholesterol. The patent describes that the formulation must contain chitosan and nicotinic acid, and additionally can contain one or more other water-soluble vitamin acid, such as ascorbic acid, folic acid, etc. The patent describes the formulation of the mixture as a powder which is then formed into tablets or packed into gelatin capsules. Of course, these tablers and capsules are as inconvenient to take as are the chitosan tablets. Also, it is well known that oral nicotinic acid (niacin) taken by itself in high doses is effective at reducing serum cholesterol and triglycenide levels. However, in therapeutic doses, niacin can have several side effects, including flushing, skin rash, liver problems, activation of peptic ulcers, gout, worsening of diabetes control, as well as others."
Certain patents disclose, among other things, chitosan that may be in a liquid formulation. The related U.S. Pat. Nos. 5,453,282, and 5,654,001 each describe a liquid chitosan formulation that contains ascorbic acid (see, e.g., Table 8 disclosing a formulation containing fruit juice (210 g/l), sugar (100 g/l), ascorbic acid (1 g/l), essence (1 g/1), and chitosan (20 g/1)) that can be used in treating obesity. However, the liquid chitosan formulation of these patents has a questionable shelf life in that the liquid contains high amounts of sugar and no preservatives. Moreover, the patents provide no teaching of ways to solubilize the chitosan in the liquid (i.e., the weight ratio of chitosan to ascorbic acid employed in Table 8 is 20:1, and no instructions are given in the patent regarding special mixing to dissolve the chitosan in the liquid), meaning the chitosan in the disclosed liquid composition likely remains in flake or powder form.
Similarly, U.S. Pat. No. 4,223,023 claims a "method of reducing lipid absorption in mammals which comprises orally administering to the mammal an amount of chitosan effective to substantially reduce the lipid absorption" (claim 1). Example 6 of this patent pertains to a chitosan powder mixture for oral administration which contains chitosan (80 g), lactose (10 g), sucrose (9.9 g), and flavor. The powder mixture is to be administered as a suspension in water, or other liquid. However, the patent provides no instruction regarding how much liquid the powder is to be added to, much less provide any instruction regarding solubilizing the chitosan in the liquid. All the remaining Examples of this patent pertain to formulations in which the chitosan is combined in the mixture with either shortening or fatty acid. Such combination will cause the precipitation of the chitosan in the composition within a short period of time.
By comparison, U.S. Pat. Nos. 4,202,881, 4,363,801, 4,474,769, and 4,512,968, and PCT International Application WO 98/32335 describe: (a) treatment of chitosan with acid, (b) rendering chitosan water-soluble by treatment with acid, and/or (c) chitosan liquid formulations. Namely, U.S. Pat. No. 4,202,881 claims a process for shampooing and conditioning hair that comprises adding to hair an aqueous solution, emulsion, or gel containing a "water soluble salt of chitosan, said chitosan salt having been prepared by reacting chitosan . . . with a sufficient amount of acid to neutralize the free amino groups present in said chitosan and to form a water soluble salt thereof" (claim 1). Col. 2., lines 23-43 describes that amino groups in chitosan can be neutralized with acids (especially with acetic acid, formic acid, and lactic acid) to obtain salts which are water soluble. The patent, however, fails to describe the process by which a chitosan-containing solution, emulsion, or gel can be obtained without adding the water-soluble salt of a chitosan to hair conditioner and/or hair shampoo.
U.S. Pat. No. 4,512,968 claims a chitosan-containing composition (including a liquid mouth rinse) for reducing dental caries (claim 1). Example 4 describes an aqueous mouth rinse formulation and Example 6 describes a liquid oral freshener. Col. 2, lines 37-47 describes that chitosan is first dissolved in inorganic weak acids to render it water-soluble. The patent, however, fails to describe the process by which a chitosan-containing composition can be obtained without including in the formulation other ingredients that impact the character of the composition (e.g., ethyl alcohol, sodium lauryl sulfonate, sodium .alpha.-olefinsulfonate, sodium lauroyl sarcosinate, and/or glycerine or other agents).
By comparison, U.S. Pat. No. 4,474,769 claims a chitosan formulation as a contraceptive. Col. 2, lines 44-53 describes that chitosan is first dissolved in weak acids (especially acetic acid, formic acid, and lactic acid). The chitosan amount can range from 10 ppm to 5%, and the amount of acidic material used to dissolve the chitosan can range from 5 ppm to 10%.
U.S. Pat. No. 4,363,801 claims a "method of treating hyperbilirubinemia which comprises orally administering to the affected patient an amount of soluble chitosan effective to substantially reduce the amount of bilirubin in the blood" (claim 1). Col. 3., lines 11-18 describes that chitosan is first dissolved in weak acids (especially acetic acid, formic acid, and citric acid) to produce a chitosan salt. The chitosan salt preferably is formed by dissolving chitosan in the weak acid, agitating the solution (e.g., in a blender), lyophilizing the solution, and pulverizing the chitosan salts produced by the lyophilization to obtain a finely ground powder. The ground powder then is mixed when ready to use with a solution of water, or other beverage.
Similarly, PCT International Application WO 98/32335 claims a chitosan solution for treating cotyledonous plants. The paragraph bridging pages 15 and 16 describes preparation of an aqueous chitosan acetate solution which exhibits sufficient longevity to be packaged in a laboratory and transported for use in the field. This solution is obtained by vigorously stirring chitosan flakes in water at a temperature of 60.degree. C., adding acetic acid with continued stirring at elevated temperature to dissolve the chitosan, filtering the solution, diluting with water, and packaging the solution.
Thus, these references disclose at most a liquid composition produced by treatment of chitosan with acid. It is not clear whether these preparations all contain chitosan in solubilized form and/or exhibit any stability. More important, since certain of these preparations contain other ingredients specific for particularized uses, its not clear whether these preparations are appropriate for human consumption in a weight treatment regimen, much less are palatable for human consumption.
Finally, PCT International Application WO 98/34625 pertains to so-called "microcrystalline chitosan" that can be employed for reducing absorption of lipids. The microcrystalline chitosan optionally is in the form of a gel-like dispersion or powder. The microcrystalline chitosan appears to be prepared by a process that involves aggregating the glucosamine macromolecules from a solution of chitosan in an acid by introduction of an alkaline solution (i.e., as described in PCT International Application 91/00298). However, it is not clear from the disclosure exactly what the characteristics of the gel should be (e.g., rigidity, etc.), and what other components optionally can be present in, or are needed for the dispersion.
"More recently, an extracted and highly refined liquid form of polyglucosamine has become available for sale, e.g., FTF Liquid Chitosan (sold by a variety of Internet vendors including Discover Nutrition, also described under the name Maderia Liquid PolyGlucosamine, marketed by Maderia, Inc. This liquid form comprises purified liquid polyglucosamine (i.e., solubilized polyglucosamine) with many of the common components of chitosan removed, that must be measured in precise quantities (e.g., an exact number of drops) into another liquid to form an all-liquid chitosan dosing solution. The product itself is a clear solution. The miscibility of the liquid chitosan in another liquid means there is no clear change in form of the solution containing chitosan as compared to the solution which does not contain chitosan. This causes consumer uncertainty as to whether the beverage being consumed truly is a chitosan-containing solution, and could conceivably lead to overdosing (e.g., as where the chitosan is added to the solution more than once). Moreover, the lack of change of form of the solution denies the consumer any clear sense of satisfaction that a chitosan-containing weight treatment solution is being imbibed. Of course, many times in a weight treatment regimen, the perception that an action is being taken and an effect will be observed as an consequence of that action, is key to obtaining a beneficial result.
Along similar lines, Collaborative Laboratories markets a polyalectrolyte composed of ascorbic acid and polyglucosamine (i.e., Ascorbyl Glucosearine.TM.). This polyelectrolyte is not described as being effective for the prevention of fat absorption (although a substantial number of its properties are described). However, if the polyclectrolyte can be so employed (e.g., in a weight treatment regimen), it suffers from the same problems as described for solubilized chitosan. Namely, the polyglucosamine is a liquid that is water-soluble."
Accordingly, the present invention provides novel chitosan-containing liquid compositions, as well as methods for their preparation and use. The chitosan-containing compositions of the invention are palatable and can be employed, inter alia, in a weight treatment program. In particular, the invention desirably provides a chitosan-containing liquid suspension composition which remains stable and is usable as an additive, for instance, in water or water-based liquids. These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.